NCT04224558

Stem Cell Transplantation in Crohn's Disease

Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 13 Years – 28 Years
• Healthy volunteers: Not accepted

Summary

Unfortunately, some patients with Crohn's disease (CD) fail to respond to the best clinical treatments and some only experience temporary benefit. For severe Crohn's disease, there is an experimental treatment called "high dose immunoablation" followed by autologous hematopoietic stem cell transplantation (HSCT). This study removes over active lymphocytes (immunoablation) and replaces them using blood stem cells that have been taken from the patient's own body. The aim of the study is to reset or reprogram the patient's immune system to its state prior to diagnosis.

Detailed description

The treatment of Crohn's disease has proven to be quite efficacious in the majority of patients with the timely use of combination therapies for remission induction (corticosteroids and/or biologics) and maintenance of disease control (immunosuppressives and/or biologics). However, a proportion of patients fail to achieve complete and long term disease control and often require multiple intestinal surgeries with a risk of developing short bowel syndrome. Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system has been proposed as an alternative strategy to induce long term disease control in this high-risk population. It has been demonstrated that despite the potential toxicity and morbidity associated with the procedure, the benefit-risk ratio is favorable. Hence, the investigators propose to offer HSCT to selected CD patients and to study mechanisms of reducing T cell autoreactivity which will hopefully lead to more focused therapeutic approaches in the future. This is an open-label, non-randomized, non-blinded, prospective study in therapeutic refractory Crohn's patients, failing conventional therapy. The primary objective is to evaluate the safety and potential clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory CD. Death (transplant-related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0) within the first 6 months after HSCT will be monitored to meet this end-point. SECONDARY OBJECTIVES 1. To evaluate the incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections. 2. To evaluate the impact of HSCT on quality of life and school productivity. 3. To elucidate the underlying mechanism involved in the observed benefit of HSCT on CD. First, the safety will be evaluated by the amount of related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at various short and long term time points. Second, to determine clinical benefit, the percentage of patients in sustained disease remission at 0, 2, 4, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a Crohn's Disease Activity Index (CDAI) \< 150 without the use of corticosteroids. In addition, mucosal healing will be assessed during ileocolonoscopy at 6 and 12 months following HSCT using the CD endoscopic index (SES). SECONDARY ENDPOINTS \- Change in Crohn's disease endoscopic index after 6 and 12 months.

Conditions

• Crohn Disease

Interventions

Type	Name	Description
DRUG	Mesna	Stem Cell Mobilization: Infused according to institutional guidelines; Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.
DRUG	Cyclophosphamide	Stem Cell Mobilization: Cyclophosphamide (CY) infused intravenously over 1 hour: 50 mg/kg (25 mg/kg/day on 2 consecutive days)
DRUG	Filgrastim	Stem Cell Mobilization: Filgrastim (G-CSF) 10 mcg/kg SC will start 5 days after the last dose of CY and will end the day before the last leukapheresis; Post-PBSC Infusion Conditioning: Filgrastim administered intravenously 5 mcg/kg IV starting day + 5, continue until ANC of \>1000/μL
PROCEDURE	Apheresis catheter placement	Subjects will require placement of an Apheresis catheter by Intervention Radiologists on the day of collection of stem cells.
PROCEDURE	Leukapheresis	Leukapheresis will be performed on a continuous flow separator machine according to institutional guidelines to target 3-8 x 10\^6 CD34+ cells/kg body weight.
DRUG	Fludarabine	Preparative/Conditioning Regime Fludarabine given as 30 mg/m2 per dose x 4 days, beginning on day -6.
DRUG	Methylprednisolone	Preparative/Conditioning Regime r-ATG pre-medication according to institutional guidelines
DRUG	Diphenhydramine	Preparative/Conditioning Regime r-ATG premedication according to institutional guidelines
DRUG	Acetaminophen	Preparative/Conditioning Regime r-ATG premedication according to institutional guidlines
DRUG	anti-thymocyte globulin (rabbit)	Preparative/Conditioning Regime r-ATG administered intravenously: 2.5 mg/kg/dose IV over 6 hours on specified days (day -6,-4,-2); ); total 3 doses=7.5 mg/kg.
DRUG	lymphocyte immune globulin	Preparative/Conditioning Regime In patients who develop severe allergic reactions to rATG (Thymoglobulin), it may be substituted by horse ATG (hATG, ATGAM, Pharmacia \& Upjohn, Kalamazoo, MI). The recommended dose of hATG is 25 mg/kg/day for 3 doses.
BIOLOGICAL	Peripheral Blood Stem Cell Infusion	PBSC (peripheral blood stem cell) infusion on day 0 as per institutional guidelines.
DRUG	Cytoxan	Post-PBSC Infusion Conditioning Cytoxan infused intravenously: 50mg/kg/day x 2 days. Infused over 2 hours with adequate hydration or according to institutional guidelines.

Timeline

• Start date: 2019-11-15
• Primary completion: 2027-09-30
• Completion: 2027-09-30
• First posted: 2020-01-13
• Last updated: 2026-02-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study